Preeclampsia remains a major cause of morbidity and mortality to both mother and unborn child in part because of the paucity of information concerning the control of normal blood pressure during pregnancy, as well as why peripheral vascular resistance increases so markedly in preeclampsia. This competitive renewal extends our original aims by focusing on mechanistic dissection of several unique observations made during the 01 and 02 years; 1) agonist induced relaxation in human omental resistance arteries is endothelium-dependent yet NO-independent and altered in normal pregnancy, 2) acetyleholine-induced relaxation of these vessels is abolished in preeclampsia while bradykinin-induced relaxation is unchanged compared with normotensive pregnancy, 3) maximal contractions are increased in preeclampsia. and 4) preeclamptic vessels exhibit characteristic phasic oscillatory activity which is both endothelium- and cyclooxygenase-dependent. Proposed for the 04-09 years are pharmacologic studies of contraction and relaxation in omental and subcutaneous resistance arteries obtained from pregnant normotensive women and patients with preeclampsia undergoing cesarian deliveries, comparing results to those from nongravid subjects and gravidas with chronic hypertension. Properties of these 200 mun arteries will be studied under isometric or flow conditions in vitro, testing the following major hypotheses: 1) Preeclampsia-induced defects in agonist and shear-stress induced endothelium-dependent relaxation will be mediated primarily by altered G-protein signaling. Such defects could occur in response to inflammatory cytokines or humoral mediators. 2) Phasic relaxation of submaximally-constricted omental resistance arteries from preeclamptic women will be mediated by oscillations of myocyte calcium and depend upon continuous enhanced synthesis of vasodilator prostaglandins by the endothelium. 3) Vessels from preeclamptic women will exhibit specific supersensitivity to AII and delayed relaxation following washout of vasoconstrictors, effects opposite to those in normal pregnancy, and both due to altered basal release of endothelium-derived vasodilators. The choice of vessels from humans reflects the fact that as yet there are no convincing animal models of preeclampsia. The focus on resistance arteries is because they are the major determinants of blood pressure. Information from these experiments should enhance our understanding of preeclampsia, and eventually lead to better methods of predicting, preventing and managing this malicious disease.